New combination of antiviral drugs can be an effective treatment
New combination of antiviral drugs can be an effective treatment

New combination of antiviral drugs can be an effective treatment

  • Researchers from the University of Pennsylvania identified a combination of antiviral drugs that they believe are effective against the SARS-CoV-2 virus.
  • The combination comprises the experimental drug brequinar with either the authorized drug remdesivir or the authorized drug molnupiravir.
  • The research group has so far only tested the drug combination in human respiratory cells and mice.
  • Researchers are planning further research that explores other drug combinations and tests through clinical trials.

After almost 2 years, the COVID-19 pandemic continues to be a problem around the world. To dateThere have been more than 414 million confirmed cases worldwide, and the disease has caused more than 5.8 million deaths.

There are currently a number of different drugs at different stages of research evaluation to test their effectiveness against SARS-CoV-2the virus that causes COVID-19.

Part of these efforts is a research team from the University of Pennsylvania that has identified a combination of antiviral drugs to treat COVID-19. The mixture contains an experimental drug called brequinar with the drugs remdesivir or molnupiravir.

So far, researchers have tested this combination on both human airway cells and in mice. They believe that the results they have seen show that the drug combination has the potential to become a promising treatment for COVID-19.

The results of this study are published in the scientific journal Nature.

As the name suggests, an antiviral drug fights viruses that enter the human body. Antiviral drugs can enter cells infected with a virus and make it harder for the virus to bind to those cells. In addition, some antiviral drugs may prevent a virus from repeating itself. Antiviral drugs also boost the body’s natural immune system, giving it an advantage in fighting a viral infection.

Because the SARS-CoV-2 virus causes COVID-19, there are currently a number of ongoing research studies on the use of various antiviral drugs to combat the disease.

For example, a new study found one combination of two specific antiviral agents can help fight SARS-CoV-2 infection. The pharmaceutical company Pfizer has also released data for one new antiviral medicine which received approval for use in the UK in October 2021.

In October 2020, the Food and Drug Administration (FDA) approved the antiviral drug remdesivir as the first treatment for COVID-19 in adults and children over 12 years of age. The FDA originally issued an emergency use permit (EUA) for the drug in May 2020.

Results from three clinical trials showed that people admitted with COVID-19 who received remdesivir had higher rates of symptom improvement compared with placebo or standard treatment only. In January 2022, FDA extended use remdesivir to certain inpatients with COVID-19 for the treatment of mild to moderate symptoms.

Remdesivir is one of the potential drug candidates that researchers from the University of Pennsylvania found during their initial screening of about 18,000 drugs.

Researchers studied the drugs for antiviral activity against live SARS-CoV-2 virus inside human airway epithelial cells. Using this method, the researchers narrowed the field to 122 drugs that “showed antiviral activity and selectivity” against SARS-CoV-2.

According to Chief Investigator Dr. Sara Cherry, professor of pathology and laboratory medicine and director of the Chemogenomic Discovery Program at the University of Pennsylvania, aimed to identify drugs with antiviral activity against SARS-CoV-2 that are active in respiratory cells. “We identified a number of drugs, including a group of nucleoside analogues, which is the largest group of approved antiviral drugs,” said Dr. Cherry MNT.

“Important, we identified the two drugs approved for COVID-19 –remdesivir and molnupiravir, which are under the EUA. ”

ONE nucleoside analog is a type of antiviral drug that mimics a human’s natural nucleoside. A nucleoside is an organic molecule in the body that consists of a nitrogen-containing base and sugar. When used to deliver an antiviral drug, a nucleoside analog enters the body and is able to penetrate cells where there is a virus. Certain compounds in the nucleoside analog are activated, causing it to become a nucleotide. Nucleotides are the building blocks of the body’s genetic DNA and RNA code.

“Finding nucleoside analogues that mimic our nucleosides and inhibitors of our enzymes that make nucleosides led us to the hypothesis that the combination may be more than the sum of their parts, [which] is synergistic, ”explained Dr. Cherry. “Synergy is difficult to find, and our discovery may lead to the use of these combinations in treatments.”

In addition, Dr. Cherry that the researchers found a number of other drugs that fall into different classes, including drugs that inhibit a person’s nucleoside biosynthesis enzymes. The nucleoside biosynthesis inhibitor, Dr. Cherry refers to is the experimental drug brequinar.

According to the study, a nucleoside biosynthesis inhibitor that brequinar stops the body from producing nucleosides. “This made sense because [SARS-CoV-2] viruses use the nucleoside building blocks created by our cells to produce the virus RNA“she added. Ultimately, brequinar helps prevent the SARS-CoV-2 virus from spreading in a person’s body through the use of their RNA.

Da Dr. Cherry and her team identified the antiviral drug combination they thought would be most effective – brequinar plus remdesivir or molnupiravir – they tested the mixture on both plated human epithelial lung cells and in mice.

Within both models, researchers observed that the drug combination of a nucleoside biosynthesis inhibitor with a nucleoside analogue led to a “significant reduction in viral replication” of SARS-CoV-2 virus.

The research team also found that adding an extra antiviral agent called Paxlovid to the mixture could provide an extra boost against the SARS-CoV-2 virus. FDA approved Paxlovid in December 2021 as the first oral treatment for mild to moderate COVID-19 in children and adults over 12 years of age with a high risk of developing serious illness.

For this study, the research team focused on testing these antiviral drug combinations in cells from a human lower respiratory tract, such as the lungs.

“We found that the combination is active in a respiratory cell line as well as in air-fluid interface cultures derived from nasal epithelium as well as from bronchial cells,” said Dr. Cherry when asked if she felt this drug treatment would also be effective in the upper respiratory tract. “Therefore, we believe that this will be active in the upper respiratory tract in humans.”

Dr. Cherry also believes that this antiviral drug combination could potentially be effective against new variants of SARS-CoV-2. “Given that these drugs target RNA replication of the virus, which does not develop rapidly, and not the Spike protein, it is likely that this combination will be active against new variants,” she explained. “We actually found that the combination showed synergy with all the variants we tested. And we are currently testing Omicron.”

Regarding the next steps for this research, Dr. Cherry that they are currently continuing to explore the use of these drug combinations as well as other drugs that the research team identified in the screening to determine how they affect SARS-CoV-2 and if they could treat COVID-19.

Researchers also mentioned that the next step in testing these drug combinations would include testing in clinical trials.

It is of interest to Dr. Fady Youssef, a board-certified pulmonologist, internist and critical care specialist at MemorialCare Long Beach Medical Center. Dr. Youssef spoke MNT about this study and said that it is encouraging to see opportunities in combinations of these antiviral drugs.

“The biggest question we have is how to identify and treat patients early in their disease state before the virus develops and causes pneumonia,” he explained. “Many of the interventions we have do not work as well once the disease has developed, including antiviral drugs. The most appropriate time to put out a fire is the earliest time you can.”

Another big question, Dr. continued. Youssef, “will be: How does this work when used in [humans]? This is a good precursor to the fact that there is a signal there that is worth testing. How it’s going to work in [humans] is unknown and how much activity it will have in the upper respiratory tract versus lower duct will depend on how it performs in human experiments. ”

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